It is a general consensus in biology that a high diversity (variation of different types of organisms) is beneficial for the global ecosystem as well as for local more limited ones, and also for the individual human being. A high diversity indicates that the ecosystem is in healthy balance. In contrast, an unbalanced or disturbed, or diseased, ecosystem opens up for “overgrowth” of a few organisms, taking over the system and causing further disturbances and new diseased conditions. This also applies to the ecosystem of the human gut.
The bacterial flora of the human gastrointestinal (GI) tract is a complex ecosystem. The composition and activity of the bacterial flora play important roles in human health due to its contribution to nutrition, development and constant tuning of the immune system, and colonization resistance. The GI tract can be regarded as a specialized tube extending from the mouth to the anus. It is divided into several well-defined anatomical regions, including mouth, oesophagus, stomach, small intestine (duodenum, jejunum and ileum), and large intestine (caecum, colon and rectum). The bacterial concentrations in the stomach and upper two thirds of the small intestine (duodenum and jejunum) are relatively low because of the acidity in the stomach, short transit time of content, secretion of bile and pancreatic juice. The concentration is normally in the range of 102 to 104 colony forming units of bacteria (cfu) per ml of gastric or intestinal content, and examples of typical resident bacteria in these regions are Streptococcus and Lactobacillus. The distal part of the small intestine (ileum) has normally a concentration of 107-108 cfu per ml and is usually dominated by the same types of bacteria that are found in colon, i.e. different classes of Firmicutes, Bacteriodetes, Fusobacteria, Verrucomicrobia, Proteobacteria and Bifidobacterium (WANG, M., AHRNÉ, S., JEPPSSON, B. & MOLIN, G. (2005). Comparison of bacterial diversity along the human intestinal tract by direct cloning and sequencing of 16S rRNA genes. FEMS Microbial Ecology 54: 219-231). The highest bacterial concentration is found in the large intestine because of the longer transit time (up to 60 h). It has been estimated that bacterial biomass makes up 40-55% of the faecal solids, and the concentration of live bacteria is normally around 1010-1011 cfu per g of intestinal content. In an undisturbed, balanced and healthy colon also the bacterial diversity is at its peak. However, due to the extremely high bacterial concentration, the colon is also the part of the GI tract that is most vulnerable for translocation where live bacteria or toxic parts of bacteria pass through the mucosal barrier and into the mesenteric lymph nodes and other extra-intestinal sites, such as the spleen, liver, kidney, peritoneal cavity and bloodstream. Low bacterial diversity (LBD) increases the risk of large intestinal bacterial overgrowth (LIBO) and small intestinal overgrowth (SIBO), which may lead to translocation.
It has been demonstrated in the technical field that the diversity of the gastrointestinal tract in patients with Crohn's disease is low, [Manichanh C., Rigottier-Gois L., Bonnaud E., Gloux K., Pelletier E., Frangeul L., Nalin R., Jarrin C., Chardon P., Marteau P., Roca J., and Doré J. (2006) Reduced diversity of faecal microbiota in Crohn's disease revealed by a metagenomic approach. Gut 55:205-211] [Ott S. J. Musfeldt M., Wenderoth D. F., Hampe J., Brant O., Fölsch U. R., Timmis K. N., and Schreiber S. (2004) Reduction in diversity of the colonic mucosa associated bacterial microflora in patients with active inflammatory disease. Gut 53:685-693].
It has further been demonstrated that newborn with a low diversity in the gastrointestinal tract run a greater risk to become allergic, [Wang, M., Karlsson, C., Olsson, C., Adlerberth, I., Wold, A., Strachan, D. P., Martricardi, P. M., Åberg, N., Perkin, M. R., Tripodi, S., Hesselmar, B., Saalman, R., Molin, G. & Ahrné, S. (2008). Reduced diversity in the early fecal microbiota of infants developing atopic eczema: Low diversity in early microbiota of infants developing atopy. Journal of Allergy and Clinical Immunology 121:129-134.
It has further been demonstrated that female rats suffering from “overgrowth” (low diversity) in the gastrointestinal tract gave birth to babies with an enhanced haptoglobin level and immature intestine, [FÅK, F., Ahrné, S., Molin, G., Jeppsson, B. & Weström, B (2008). Microbial manipulation of the rat dam changes bacterial colonization and alters properties of the gut in her offspring. American Journal of Physiology—Gastrointestinal and Liver Physiology 294: 148-154.
Thus, there seems to be a connection between low diversity in the gastrointestinal tract and several physiologically disturbed conditions in human beings and other mammals.
It is known that the use of antibiotics lowers the bacterial diversity in the gastrointestinal tract. Since the use of antibiotics is huge worldwide there is indeed a need within the technical field to provide novel ways to overcome this problem of low diversity in the gastrointestinal tract, said low diversity affecting the general health of mankind.
It is further generally known that the lifestyle of mankind in developed countries causes many unhealthy disturbances and conditions such as cardiovascular diseases in view of e.g. stress and overweight. It is known that people with these disturbances and conditions often have a low bacterial diversity in the gastrointestinal tract.
Thus, there is a need within the technical field to overcome the problem of physiologically disturbed conditions related to or due to low diversity in the gastrointestinal tract of individuals.
WO 01/11077 A2 discloses methods of diagnosing or treating irritable bowel syndrome and other disorders caused by small intestinal bacterial overgrowth (SIBO) by administration of anti-microbial or probiotic agents, e.g. a species of Bifidobacterium or Lactobacillus, or normalizing intestinal motility by employing a prokinetic agent.